Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence exists for a negative correlation between Parkinson's disease and smoking. The present and previous studies indicate that nicotine treatment can markedly alter the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in the black mouse based on biochemical determinations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in neostriatum and substantia nigra 2 weeks after MPTP injection. Acute intermittent treatment with (-)nicotine starting 10 min before the MPTP injection partly protected against MPTP-induced neurotoxicity in the neostriatum and substantia nigra. Also, a partial protection was observed in the substantia nigra when (-)nicotine was given together with MPTP in an acute intermittent treatment schedule. Conversely, chronic infusion of (-)nicotine via minipumps produced a dose-related enhancement of MPTP-induced DA neurotoxicity in the neostriatum. It is suggested that the protective activity of nicotine in the MPTP model is related to a blockade of MPP+ uptake into the DA cells via increased DA release. Conversely, the nicotine enhancement of MPTP-induced DA toxicity is suggested to be caused by a failure of the nicotinic cholinoceptors to desensitize to the chronic (-)nicotine exposure, leading to increased chronic influx of Na+ and Ca2+ ions via the ion channels of the nicotinic cholinoceptors located on the DA neurons with associated increased Ca ion toxicity and increased energy demands.
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PMID:Differential effects of acute and chronic nicotine treatment on MPTP-(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced degeneration of nigrostriatal dopamine neurons in the black mouse. 152 Oct 37

Studies have shown that severe daytime restriction of dietary protein improves the efficacy of L-dopa and reduces response fluctuations in some Parkinson's disease (PD) patients. This study investigated the nutritional adequacy of the daytime restricted-protein diet. Eleven free-living PD patients suffering from unpredictable response fluctuations to L-dopa were counseled to limit protein intake to approximately 10 g before 1700. Three sets of 6-d food records obtained during the 8-wk study showed that while on the test diet, mean intakes of most nutrients remained above the recommended nutrient intakes, although significant decreases occurred in protein, calcium, iron, phosphorus, riboflavin, and niacin intakes. The impact of the test diet on nutritional status as evaluated by changes in body weight and serum prealbumin was small. We conclude that healthy and highly motivated patients can maintain adequate intakes of most nutrients while restricting daytime protein intake. However, nutrient intakes might be compromised in patients whose regular diets are marginally adequate.
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PMID:Effect of daytime protein restriction on nutrient intakes of free-living Parkinson's disease patients. 155 46

Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors.
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PMID:Iron in brain function and dysfunction with emphasis on Parkinson's disease. 164 57

There is evidence to suggest that glutamate and other excitatory amino acids play an important role in the regulation of neuronal excitation. Glutamate receptor stimulation leads to a non-physiological increase of intracellular free Ca2+. Disturbed Ca2+ homeostasis and subsequent radical formation may be decisive factors in the pathogenesis of neurodegenerative diseases. Decreased glutamatergic activity appears to contribute to paranoid hallucinatory psychosis in schizophrenia and pharmacotoxic psychosis in Parkinson's disease. It has been suggested that a loss of glutamatergic function causes dopaminergic over-activity. Imbalances of glutamatergic and dopaminergic systems in different brain regions may result in anti-akinetic effects or the occurrence of psychosis. The simplified hypothesis of a glutamatergic-dopaminergic (im)-balance may lead to a better understanding of motor behaviour and psychosis.
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PMID:Glutamate receptor antagonism: neurotoxicity, anti-akinetic effects, and psychosis. 168 83

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) gives rise to motor deficits in humans and other primates which closely resemble those seen in patients with Parkinson's disease. These deficits are associated with a relatively selective loss of cells in the pars compacta of the substantia nigra and severe reductions in the concentrations of dopamine, noradrenaline and serotonin in the striatum. Similarly, in mice of various different strains the administration of MPTP also induces a marked loss of dopaminergic cells with severe depletion of biogenic amines, but higher doses of MPTP are required to produce these effects in mice than in primates. This review summarises advances made in understanding the biochemical events which underlie the remarkable neurotoxic action of MPTP. Major steps in the expression of neurotoxicity involve the conversion of MPTP to the toxic agent 1-methyl-4-phenylpyridinium ion (MPP+) by type B monoamine oxidase (MAO-B) in the glia, specific uptake of MPP+ into the nigro-striatal dopaminergic neurones, the intraneuronal accumulation of MPP+, and the neurotoxic action of MPP+. This is exerted mainly through the inhibition of the enzymes of the respiratory chain (Complex I), the disturbance of Ca2+ homeostasis, and possibly by the formation of free radicals. The relevance of the MPTP model to idiopathic Parkinson's disease is discussed.
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PMID:MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease. 181 82

The contents of indispensable major elements sodium (Na), phosphorus (P), calcium (Ca), magnesium (Mg), trace elements iron (Fe), copper (Cu), nickel (Ni), zinc (Zn), strontium (Sr), vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), and other elements lead (Pb), silicon (Si), aluminium (Al), titanium (Ti), barium (Ba), lanthanum (La), cadmium (Yb), cerium (Ce), scandium (Sc), silver (Ag), in cerebrospinal fluid (CSF) were measured in 13 patients suffering from Parkinson disease before and after autotransplantation of adrenal medulla. It was found that while the patients' objective symptoms were relieved and the contents of monoamine transmitters were changed, the contents of P, V, Co, Cr, in CSF increased significantly (P less than 0.05 or 0.01) at the first, 2nd, 4th, 6th, and 8th week, the contents of Mn in CSF also increased significantly at the first 4th week (P less than 0.05) but decreased significantly at the 8th week the contents of Zn in CSF increased significantly (P less than 0.05) at the 2nd week; Mo increased significantly (P less than 0.05 or 0.01) at the 4th and 8th week B increased significantly (P less than 0.05) at the first week; the contents of Ca, Na, Sr, Ba, Al, Ti, La, Ce, Yb, Sc, Ag in CSF increased significantly (P less than 0.05 or 0.01) at the 8th week, Mg, Fe, Cu Ni, Pb, Si, Cd remained unchanged after operation. The results suggest that the contents of these chemical elements can be affected by this kind of operation, indicating that these elements are involved in the pathogenesis of Parkinsonism.
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PMID:[Determination of multiple chemical elements in CSF in Parkinson disease after intracerebral autotransplantation of the adrenal medulla]. 186 88

Amino acids such as L-glutamate und L-aspartate are major excitatory neurotransmitters in the mammalian central nervous system (CNS) and potential neurotoxins (excitotoxins), which can destroy central neurons by excessive activation of respective receptors. In the last three decades evidence has accumulated that excitatory amino acids (EAA) are involved in many neurological diseases and that pharmacological intervention offers prospects of novel and more effective therapies. Three different receptor types for EAA have been identified, each being named by the selective agonist to which it is preferentially sensitive, i.e. N-methyl-D-aspartate- (NMDA), kainate- and quisqualate-receptors. In this review interest is focused primarily on the NMDA-receptor, whose structure has been subject of numerous electrophysiological and biochemical studies. Today, it is well established that the NMDA-receptor-ionophore complex has an agonist binding site for glutamate, NMDA and related EAAs which is coupled with an ion channel permeable to Na+, K+, Cl- and Ca2+. Four other binding sites for glycine, phencyclidine, Mg2+ and Zn2+ have been identified which can differentially modulate the function of the NMDA receptor. An additional polyamine binding site has recently been reported. Numerous studies on experimental animals demonstrate that modulators of NMDA-mediated neurotransmission may have antiepileptic, anxiolytic, muscle-relaxant and memory-enhancing effects. Particular interest has gained the possible neuroprotective efficacy of NMDA-receptor antagonists in neurological diseases such as hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS encephalopathy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The N-methyl-D-aspartate receptor complex. Various sites of regulation and clinical consequences]. 197 26

A 53-year-old woman is reported with recurrent cerebrovascular disease, pseudohypoparathyroidism and dural calcification without basal ganglia calcification. She had typical clinical and laboratory features of pseudohypoparathyroidism and a family history of the condition. One case has been reported previously with pseudohypoparathyroidism and Parkinson's disease without basal ganglia calcification. Patients with widespread intracranial calcification should be evaluated for underlying abnormalities in calcium metabolism. Calcium supplementation and administration of vitamin D frequently correct the metabolic abnormality and halt clinical progression.
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PMID:Pseudohypoparathyroidism and cerebrovascular disease with dural calcification. 200 28

Recent evidence suggests that iron accumulates in substantia nigra pars compacta of patients with Parkinson's disease (PD). This finding is compatible with changes in the respiratory chain activity, increase of malondialdehyde concentration (a measure of lipid peroxidation), decrease of enzyme activity of enzymes involved in detoxication of hydrogen peroxide and oxygen radical species, increased MAO-B-activity in this brain area etc. All these data suggest that oxidative stress may play a certain role in the pathobiochemistry of PD. In addition to the description of the neuroprotective mechanism of the MAO-B-inhibitor L-deprenyl a new aspect focuses the role of the endogenous MAO-B substrates "polyamines" which occur both in neurons and glia. A further aspect of this review deals with the role of calcium as cellular toxin. Although of major importance it is not decided yet whether these biochemical changes are primary or secondary importance to the pathogenesis of PD.
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PMID:The role of monoamine oxidase, iron-melanin interaction, and intracellular calcium in Parkinson's disease. 208 94

The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50-88%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60-88%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.
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PMID:Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases. 214 Aug 97


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